Phosphatidylserine accelerates wound healing and reduces necrosis in the rats: Growth factor activation.

To examine the effect of topical phosphatidylserine (PS) on wound healing factors and tissue necrosis in in vivo models. Topical PS was applied to evaluate aspects of the wound healing process and growth factors production of vascular endothelial growth factors (VEGF) as well a necrosis reduction in the skin flap of rat models. Moreover, phenytoin (PHT) and cyclosporine A (CsA) were used topically as positive control treatments in wound and necrosis models, respectively. Immunohistochemistry (IHC) VEGF, transforming growth factor-ß (TGF-ß), fibroblast growth factor (FGF) and histopathology were analysed on the wounds of rats. In the necrosis assessment, necrotic areas were determined on photography taken from the back skin of rats. Results indicated that PS topically enhanced significantly (P < 0.05) numbers of fibroblasts and endothelium while inhibiting the neutrophils and macrophages during the 14 days of wound treatment. Moreover, higher values of collagen deposition and epithelialization scores as well as wound recovery percentage (near 80%) were determined significantly (P < 0.05) in the PS group compared with the control. IHC analysis determined that FGF and VEGF cytokine factors were elevated in the wound site by topical PS. Moreover, the necrotic area was significantly (P < 0.05) improved in the PS group. Our experiment indicated that wound improvement and flap survival values in PS treatments were superior to PHT and CsA control groups, respectively. In conclusion, these findings suggest the potential of PS application in the healing of wounds and control of necrosis development after surgery or skin injuries.

Evaluation of the effect of heat shock protein 70 targeted drugs on cirrhotic cardiomyopathy in biliary cirrhotic rats.

AIMS: Liver cirrhosis leads to cirrhotic cardiomyopathy (CCM) and chronotropic incompetence (CI). Heat shock protein 70 (Hsp70) regulates cellular apoptosis and autophagy in stress. Teprenone modulates the Hsp70 and protects against cellular injury. Thus, we aimed to evaluate the effect of teprenone on CI in biliary cirrhotic rats. MAIN METHODS: Liver cirrhosis was induced in male Wistar rats through bile duct ligation (BDL). The chronotropic responses and QT interval were studied through electrocardiography (ECG) in sham, cirrhotic, and cirrhotic/teprenone (100 mg/kg) pre-treated groups. Brain natriuretic peptide (BNP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and monocyte chemo-attractant protein-1 (MCP-1), and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were investigated in serum. The Hsp70, B-cell lymphoma 2 (Bcl-2), and B-cell lymphoma 2-associated X protein (Bax) expressions were quantified through real-time polymerase chain reaction (Real-time PCR). KEY FINDINGS: The chronotropic responses were decreased significantly in cirrhotic and cirrhotic/teprenone groups. The QT interval and serum BNP, TNF-α, IL-6, ALT, AST, and MCP-1 levels were increased significantly in the cirrhotic and decreased significantly, except BNP, in the cirrhotic/teprenone group. The Hsp70 and Bax expressions increased significantly in cirrhotic and decreased significantly in the cirrhotic/teprenone group while the Bcl-2 decreased significantly in cirrhotic and increased significantly in the cirrhotic/teprenone group. SIGNIFICANCE: Teprenone does not relieve the CI and BNP changes in CCM while other indices are treated. Given that CCM is a multifactorial disease and needs to target other genes and proteins concurrent with Hsp70 to relieve CCM.

Neuroprotective phosphatidylserine liposomes alleviate depressive-like behavior related to stroke through neuroinflammation attenuation in the mouse hippocampus.

OBJECTIVE: To investigate the protective effect of phosphatidylserine liposomes (PSL) on post-stroke (ST) injuries such as neuroinflammation and depression in mice. METHODS: Brain ischemia was induced via the right unilateral common carotid artery occlusion model. Then, behavioral assessments including the forced swimming test (FST) and tail suspension test (TST) were used to evaluate the antidepressant-like effect of PSL. Moreover, inflammatory cytokines changes in the hippocampus including TNF-α and IL-10 levels as well as the number of survived neurons were evaluated in ST mice using immunohistochemistry (IHC). RESULTS: A significant reduction of the immobility time in both behavioral tests indicated the antidepressant activity of PSL. Moreover, the number of viable neurons increased significantly with PSL treatment, which was similar to control group, compared to the untreated ST group. IHC analysis of ST mice receiving PSL showed a significant reduction in TNF-α and IL-10 levels in the inflamed hippocampus of mice. CONCLUSION: Oral PSL may improve post-stroke depression (PSD) through its anti-inflammatory properties.

Evaluation of ROCEN on Burn Wound Healing and Thermal Pain: Transforming Growth Factor-ß1 Activation.

The present study aimed to evaluate the effect of liposomal arthrocen 2% (ROCEN) on the healing of burn wound and pain alleviation of thermal stimuli in a rat model of the second-degree burn. The results showed that ROCEN formulation significantly improved the main parameters of burn wound healing in a short period of time (7 days). The percentage of wound surface was also reduced significantly compared with the control group following once daily application of ROCEN for 14 days. The level of TGF (transforming growth factor)-ß1 cytokine was also elevated significantly in the burn tissue treated with ROCEN almost the same as zinc oxide cream. Also, ROCEN showed a significant analgesic effect evaluated by 2 models of acute thermal pain, tail-flick and hotplate tests, which suggested that the formulation may act as a pain reliever in burn injuries. In conclusion, the application of the topical formulation of ROCEN may have benefits in the acceleration of the wound healing process and alleviation of the pain due to burn injuries.

Metformin loaded phosphatidylserine nanoliposomes improve memory deficit and reduce neuroinflammation in streptozotocin-induced Alzheimer's disease model.

Alzheimer's disease (AD) is closely associated with neuroinflammation development in the brain. Co-delivery of metformin (MET) with phosphatidylserine liposomes neuroprotectant may be beneficial in ameliorating AD-related symptoms like memory impairment and inflammation. Therefore, we aimed to prepare metformin containing phosphatidylserine nanoliposomes formulation (MET-PSL) and to evaluate its effect on rats subjected to AD. Alzheimer's disease model was induced by bilateral intracerebroventricular injection of streptozotocin (3 mg/kg) into rat brains using the stereotactic technique. MET-PSL, MET, and PSL alone were administered intraperitoneally to AD-induced animals and factors including learning and memory storage in addition to cytokine and tissue inflammatory changes were evaluated after a 22-day experiment period. The learning and memory parameters significantly (P < 0.05) improved in AD-rats treated with MET-PSL. Moreover, MET-PSL administration significantly (P < 0.05) decreased cytokine levels of IL1-ß, TNF-α, and TGF-ß in hippocampal tissues of rats with AD. Histological results indicated a considerable reduction in inflammatory and necrotic neural cells along with significantly (P < 0.05) increased neurogenesis in MET-PSL treated rats. Furthermore, our results showed that MET-PSL formulation could potentially act better than the free form of MET and PSL alone in the recovery process of rats with AD. In general, our data suggest that combination therapy of metformin loaded phosphatidylserine liposomes may enhance the therapeutic performance in AD patients of a clinical study.

In vitro antioxidant activity and in vivo wound-healing effect of lecithin liposomes: a comparative study.

Aim: This study was conducted to determine the potentials of egg lecithin (egg-l) and soy lecithin (soy-l) liposomes in antioxidative and wound healing properties. Materials & methods: The suspensions of egg-l and soy-l were prepared using the fusion technique. The free radical scavenging activity of both lecithin liposomes was evaluated by DPPH and ABTS methods. Tissue staining was used to assess wound-healing parameter. Results: Liposomal lecithins showed an increasing trend of 1-10 mg/ml in radical-scavenging activities (p < 0.0001). Wound-healing assessments showed a significant effect (p < 0.0001) in treatment with topical lecithin liposomes. The results of wound healing also showed better outcomes of egg-l in comparison with phenytoin 1% cream. Conclusion: Antioxidant lecithin liposomes may enhance the treatment of wound injuries.